13TSB_SynBio: Rapid Engineering of Cellular Factories
Lead Research Organisation:
University College London
Department Name: Biochemical Engineering
Abstract
This project will integrate a number of novel synthetic biology technologies in a demonstration project to rapidly engineer a cellular factory. This includes a novel biopump from UCL which will allow the selective import of a hydrophobic substrate into the cell, where a short synthetic pathway will transform it into a higher value aroma chemical, before the final specialty chemical product is exported from the cell. This short synthetic pathway will be rapidly optimized by a combination of a novel gene expression control technology, RiboTite, from University of Manchester and the statistical optimization technology of Synthace. A successful outcome is expected to both yield a process for the production of a high value specialty chemical, as well as a demonstration of a new methodology for the rapid engineering of a bioprocess.
Technical Summary
This project will integrate a number of novel synthetic biology technologies in a demonstration project to rapidly engineer a cellular factory. This includes a novel biopump from UCL which will allow the selective import of a hydrophobic substrate into the cell, where a short synthetic pathway will transform it into a higher value aroma chemical, before the final specialty chemical product is exported from the cell. This short synthetic pathway will be rapidly optimized by a combination of a novel gene expression control technology, RiboTite, from University of Manchester and the statistical optimization technology of Synthace. A successful outcome is expected to both yield a process for the production of a high value specialty chemical, as well as a demonstration of a new methodology for the rapid engineering of a bioprocess.
Planned Impact
WHO WILL BENEFIT: Platform and fine chemical companies, biotech companies and contract manufacturing organisations charged with producing fine and platform chemicals on the multi-kilo and -ton scale, in particular the project partner Synthace. Additionally, many chemical companies that employ biocatalysts, such as DSM, Lonza, BASF and Dr. Reddy's, could also benefit from the technologies developed here. Similarly, oil companies such as Shell and BP have invested heavily in synthetic biology programmes to engineer bacteria to produce new biofuels, where new-engineered microbial factories would be equally important. Any number of these companies could benefit through licensing agreements to use new systems based on the technologies developed in this project.
HOW WILL THEY BENEFIT: We will actively seek to communicate our findings to the wider community through scientific meetings and scholarly publications. However, in order for the technology we develop to become widely adopted, particularly in industry, it will be important to first secure any intellectual property rights for all new inventions we discover. As the research progresses and our relationships with interested commercial partners develop, and whilst working within the conditions of the TSB grant, we will seek to commercially exploit these new technologies and license on IP for use in industrial-scale chemical production processes. Improvements in cell line platform development and bioprocess efficiency, generated from this project, could lead to alternative sustainable sources for chemical production, and reduce the reliance upon petrochemical feedstocks, leading to associated potential environmental benefits. This research project will also generate technology and knowledge that will help maintain the UK's competitive edge and will produce highly trained and skilled research personnel.
HOW WILL THEY BENEFIT: We will actively seek to communicate our findings to the wider community through scientific meetings and scholarly publications. However, in order for the technology we develop to become widely adopted, particularly in industry, it will be important to first secure any intellectual property rights for all new inventions we discover. As the research progresses and our relationships with interested commercial partners develop, and whilst working within the conditions of the TSB grant, we will seek to commercially exploit these new technologies and license on IP for use in industrial-scale chemical production processes. Improvements in cell line platform development and bioprocess efficiency, generated from this project, could lead to alternative sustainable sources for chemical production, and reduce the reliance upon petrochemical feedstocks, leading to associated potential environmental benefits. This research project will also generate technology and knowledge that will help maintain the UK's competitive edge and will produce highly trained and skilled research personnel.
Publications
Baganz F
(2016)
Building effective microbial cell factories for production of fuels and chemicals with the aid of transport proteins
in New Biotechnology
Call TP
(2016)
Modulating the import of medium-chain alkanes in E. coli through tuned expression of FadL.
in Journal of biological engineering
Grant C
(2014)
Identification and use of an alkane transporter plug-in for applications in biocatalysis and whole-cell biosensing of alkanes.
in Scientific reports
Grant C
(2014)
Use of transporter plug-ins in building effective microbial cell factories for chemical and fuel production
in New Biotechnology
Description | As part of this collaborative TSB feasibility study we evaluated a small library of transporter proteins for building an optimised bacterial strain capable of efficiently utilising fatty acid based feedstocks and removing the final product to avoid problems such as inhibition, toxicity or unfavourable equilibrium. Specifically we: 1. Developed a screen for rapid testing of transporter proteins for uptake of oleic, linoleic and linolenic acid 2 Designed and characterised additional transporter proteins for compounds of interest 3 Developed screen for rapid testing of transporters for removal of target product (short chain alcohol) 4. Demonstrated feasibility of using both importer and exporter with metabolic synthesis pathway |
Exploitation Route | New research grants, academic and industrial collaborations |
Sectors | Chemicals,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
Description | The strains and transporter protein plasmids have been assessed by the industrial project partner Synthace. |
First Year Of Impact | 2015 |
Sector | Chemicals,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
Impact Types | Economic |
Description | CSC-UCL Joint Research Scholarship |
Amount | £66,540 (GBP) |
Organisation | University College London |
Sector | Academic/University |
Country | United Kingdom |
Start | 10/2016 |
End | 09/2019 |
Description | Combined engineering and biological approaches to improve the efficiency of isobutanol production |
Amount | £95,600 (GBP) |
Funding ID | NAF\R2\180721 |
Organisation | The Royal Society |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 12/2018 |
End | 11/2022 |
Title | Biopump plasmids |
Description | Plasmid vectors coding for different outer membrane proteins expressed under the control of a rhamnose-inducible promotor. |
Type Of Material | Biological samples |
Year Produced | 2014 |
Provided To Others? | Yes |
Impact | Improvement in rates of whole cell biocatalysis by >10 fold. Improvement of bioalkane synthesis by >5fold. Successful demonstration of controlled expression using regulatory RNA elements (riboswitch). |